Not according to a couple of papers published online during the holiday-shortened week. The work suggests torcetrapib’s problems were independent of its effects on cholesterol. “Torcetrapib’s failure is based on the drug’s off-target toxicity,” Menno Vergeer, one of the researchers, told the heartwire, which summarizes the findings. “I think that’s the most important conclusion we both arrive at.”

Vegeer’s group found that higher HDL levels in patients taking torcetrapib didn’t lead to smaller plaques in the carotid artery, indicating the drug didn’t work as hoped. Their analysis found the torcetrapib patients had higher blood pressure and related changes in electrolytes.

A second paper focused on patients whose coronary arteries were examined with ultrasound in a trial called Illustrate. And the researchers, including Steven Nissen from the Cleveland Clinic, found that patients who had the biggest increase in HDL had the most regression of the plaques in their arteries. So Nissen told the heartwire, CETP inhibitors that don’t have torcetrapib’s problems might be useful after all. Keep an eye on anacetrapib from Merck and dalcetrapib from Roche.

Of course, the unexpected increase in mortality in the big torcetrapib study mean that any similar drug would face a tough road with regulators. That would mean large, lengthy trials to demonstrate the medicines don’t have unexpected baggage.

Comments (5 of 5)

Wlecome to the challenges of pharmaceutical research. Pharmacogenomic evidence originally led Pfizer to hope that elevating HDL through inhibiting CETP would be beneficial. A biomarker assessment in patients suggests that plaque reduction is associated with the highest HDL elevations. Yet, with torcetrapib, there appears to be a safety biomarker popping up. Are either the efficacy or safety signals really biomarkers of long term clinical outcome? You only need to ante up $800M to run mortality and morbidity trials for 5 or more years. Any investors?

5:11 pm December 1, 2008

Dr Peters wrote :

Steve Nissen picked up not only the COX-2 inhibitor scandal, but also the Avandia disaster. The fact that he has saved possible millions from adverse consequences really gets to you Pharma whores, doesn't it?

10:17 am December 1, 2008

Anonymous wrote :

Steve Nissen more than just about anyone on the planet has done more to crush cardiology research and leave no option cardiology patients with very dim prospects. All of this to boost his self-serving ego. Get a life man!

9:29 am December 1, 2008

Giveme a Break wrote :

Steve Nissen is a joke!!! Please dont give a spin, like the big pharma, about other drugs of this class may be useful!!